M. Feuerstein et al. / Tetrahedron Letters 42 (2001) 5659–5662
5661
B(OH)2
B(OH)2
[
Pd]*
+
+
OHC
+ OHC
OHC
Br
O
O
O
K CO
2
3
F
OMe
3
h
F
OMe
3
2
33
49%
1
mmol.
2 mmol.
2 mmol.
51%
conversion: 81%
*
ratio substrate/catalyst: 1 000 000
Scheme 2.
Pyridines and pyrimidines are p-electron deficient hete-
rocycles. Thiophenes and furanes are p-electron exces-
Acknowledgements
1
sive. Oxidative addition to palladium should be faster
with p-electron deficient heterocycles; however, we
observed generally higher reaction rates with p-electron
excessive heterocycles. This observation suggests that
the oxidative addition of the aryl bromide is not the
rate-limiting step with this catalyst.
We thank the CNRS for providing financial support
and M.F. is grateful to the Minist e` re de l’Education
Nationale, de la Recherche et de la Technologie for a
grant.
Next, we tried to evaluate the influence of the sub-
stituents on the boronic acid on the rate of this reac-
tion; therefore, we investigated the coupling of
References
1
2
. For examples of palladium cross-coupling with heteroaro-
matic compounds, see: Li, J. J.; Gribble, G. W. Palladium
in Heterocyclic Chemistry; Pergamon: Amsterdam, 2000.
. For reviews on the cross-coupling of aryl bromides with
arylboronic acids, see: (a) Suzuki, A. J. Organomet. Chem.
4-fluoro-, 4-methoxy- and 3-(trifluoromethyl)benzene
boronic acids 14–16 with heteroaryl bromides. Lower
reaction rates were observed with all these function-
alised arylboronic acids than with simple phenylboronic
acid 13. Coupling of 14–16 with 3-bromopyridine 3 led
to products 19–21 with TONs of 96 000, 120 000 and
1
999, 147; (b) Suzuki, A. Metal-catalysed Cross-coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley: New
York, 1998; (c) Malleron, J.-L.; Fiaud, J.-C.; Legros, J.-Y.
Handbook of Palladium-catalysed Organic Reactions; Aca-
demic Press: San Diego, 1997; (d) Miyaura, N.; Suzuki, A.
Chem. Rev. 1995, 95, 2457.
. For a review on biaryl synthesis via cross-coupling, see:
Stanforth, S. Tetrahedron 1998, 54, 263.
. For examples of efficient catalysts for Suzuki cross-cou-
pling, see: (a) Beller, M.; Fischer, H.; Herrmann, A.; O
K.; Brossmer, C. Angew. Chem., Int. Ed. Eng. 1995, 34,
848; (b) Albisson, D. A.; Bedford, R. B.; Lawrence, S. E.;
Scully, P. N. Chem. Commun. 1998, 2095; (c) Wolfe, J.;
Singer, R.; Yang, B.; Buchwald S. J. Am. Chem. Soc. 1999,
7
10 000, respectively. Coupling with 12 led to adducts
32–34 with TONs of 620 000, 710 000, 880 000, respec-
tively. In order to have a more accurate idea of the
influence of the electronic factor on the rate of this
reaction we performed a competitive reaction using an
equimolar mixture of 14 and 15 in the presence of aryl
bromide 12 (Scheme 2). We observed the formation of
an almost equimolar mixture of coupling products 32
and 33. This result seems to indicate that the lower
reaction rates observed with functionalised arylboronic
acids more likely comes from partial poisoning of the
catalyst rather than from electronic factors.
3
4
8
fele,
1
1
21, 9550; (d) Weissman, H.; Milstein, D. Chem. Commun.
Finally, in order to present a simple procedure using a
commercially available ligand, we performed a few
reactions with dppe. Palladium catalyst prepared with
dppe as ligand is less active than with 1 by a factor of
ten; however, dppe–Pd complex is much more stable
and efficient than the popular but unstable catalyst
Pd(PPh ) . With dppe TONs of 82 000, 83 000 and
1999, 1901; (e) Wolfe, J.; Buchwald S. Angew. Chem., Int.
Ed. Eng. 1999, 38, 2413; (f) Zapf, A.; Beller, M. Chem.
Eur. J. 2000, 6, 1830; (g) McGuiness, D.; Cavell, K.
Organometallics 2000, 19, 741; (h) Bedford, R.; Welch, S.
Chem. Commun. 2001, 129.
. For recent examples of Suzuki cross-coupling with het-
eroaromatics, see: (a) Zhang, H.; Kwong, F. Y.; Tian, Y.;
Chan, K. S. J. Org. Chem. 1998, 63, 6886; (b) Sava, X.;
Ricard, L.; Mathey, F.; Le Floch, P. Organometallics 2000,
5
3
4
870 000 were obtained with substrates 3, 7 and 12,
respectively.
1
2
9, 4899; (c) Liu, Y.; Gribble, G. W. Tetrahedron Lett.
000, 41, 8717; (d) Cooke, G.; Augier de Cremiers, H.;
In conclusion, Tedicyp–palladium complex provides a
convenient catalyst for the cross-coupling of heteroaro-
matics with arylboronic acids. In the presence of this
catalyst heteroaromatics, such as pyridines, quinolines,
thiophenes, an indole or a furane, led to the coupling
products in good yields. The reaction can be performed
with as little as 0.00001% catalyst. This procedure
represents an environmentally friendly method for the
preparation of heterobiaryl compounds.
Rotello, V.; Tarbit, B.; Vanderstraeten, P. Tetrahedron,
2001, 57, 2787.
6. For a review on the synthesis of polypodal diphenylphos-
phine ligands, see: Laurenti, D.; Santelli, M. Org. Prep.
Proc. Int. 1999, 31, 245.
7. (a) Laurenti, D.; Feuerstein, M.; P e` pe, G.; Doucet, H.;
Santelli, M. J. Org. Chem. 2001, 66, 1633; (b) Feuerstein,